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G‐proteins and G‐protein subunits mediating cholinergic inhibition of N‐type calcium currents in sympathetic neurons
Author(s) -
Delmas Patrick,
Abogadie Fe C.,
Dayrell Mariza,
Haley Jane E.,
Milligan Graeme,
Caulfield Malcolm P.,
Brown David A.,
Buckley Noel J.
Publication year - 1998
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1046/j.1460-9568.1998.00170.x
Subject(s) - muscarinic acetylcholine receptor , gq alpha subunit , protein subunit , postsynaptic potential , microbiology and biotechnology , g protein , biology , cholinergic , acetylcholine receptor , sympathetic ganglion , protein kinase a , acetylcholine , chemistry , receptor , neuroscience , phosphorylation , signal transduction , endocrinology , biochemistry , gene
One postsynaptic action of the transmitter acetylcholine in sympathetic ganglia is to inhibit somatic N‐type Ca 2+ currents: this reduces Ca 2+ ‐activated K + currents and facilitates high‐frequency spiking. Previous experiments on rat superior cervical ganglion neurons have revealed two distinct pathways for this inhibitory action: a rapid, voltage‐dependent inhibition through activation of M 4 muscarinic acetylcholine receptors (mAChRs), and a slower, voltage‐independent inhibition via M 1 mAChRs (Hille (1994) Trends in Neurosci ., 17, 531–536]. We have analysed the mechanistic basis for this divergence at the level of the individual G‐proteins and their α and βγ subunits, using a combination of site‐directed antibody injection, plasmid‐driven antisense RNA expression, over‐expression of selected constitutively active subunits, and antagonism of endogenously liberated βγ subunits by over‐expression of βγ‐binding β‐adrenergic receptor kinase 1 (βARK1) peptide. The results indicate that: (i) M 4 mAChR‐induced inhibition is mediated by G oA; (ii) α and βγ subunits released from the activated G oA heterotrimer produce separate voltage‐insensitive and voltage‐sensitive components of inhibition, respectively; and (iii) voltage‐insensitive M 1 mAChR‐induced inhibition is likely to be mediated by the α subunit of G q . Hence, Ca 2+ current inhibition results from the concerted, but independent actions of three different G‐protein subunits.